高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (6): 1205-1211.doi: 10.7503/cjcu20180201

• 物理化学 • 上一篇    下一篇

不同力场对B-DNA到A-DNA构型转变的影响

张宏1, 蔡文生1(), 邵学广1,2   

  1. 1.南开大学化学学院分析科学研究中心, 天津市生物传感与分子识别重点实验室, 天津化学化工协同创新中心
    2.药物化学生物学国家重点实验室, 天津 300071
  • 收稿日期:2018-03-16 出版日期:2018-06-10 发布日期:2018-05-22
  • 基金资助:
    国家自然科学基金(批准号: 21773125)资助.

Effect of Different Force Fields on B-DNA to A-DNA Conversion

ZHANG Hong1, CAI Wensheng1,*(), SHAO Xueguang1,2   

  1. 1. Research Center for Analytical Sciences, College of Chemistry, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Collaborative Innovation Center of Chemical Science and Engineering(Tianjin)
    2. State Key Laboratory of Medicinal Chemical Biology, Nankai University,Tianjin 300071,China
  • Received:2018-03-16 Online:2018-06-10 Published:2018-05-22
  • Contact: CAI Wensheng E-mail:wscai@nankai.edu.cn
  • Supported by:
    † Supported by the National Natural Science Foundation of China(No. 21773125).

摘要:

采用分子动力学模拟方法比较了最新版CHARMM和AMBER(包括bsc1和OL15)力场对水溶液中B-DNA到A-DNA转化过程的影响, 利用扩展自适应偏置力(eABF)方法计算了转化过程的自由能变化. 研究结果表明, 在不同力场下, 水环境中的DNA最稳定结构存在差异, AMBER力场比CHARMM力场更符合实验结果. AMBER力场下DNA最稳定结构的小沟较窄, 稳定于B构型; 而CHARMM力场下DNA最稳定结构的小沟较宽, 介于B构型与A构型之间. 通过分析DNA周围离子及水的分布情况发现, CHARMM力场下DNA小沟周围的离子密度明显低于AMBER力场, 不能很好地抵消2条磷酸骨架之间的排斥作用, 这是CHARMM力场下小沟较宽且趋向A构型的主要原因.

关键词: B-DNA, A-DNA, 构型转变, CHARMM力场, AMBER力场, 自由能计算

Abstract:

The aim of the present work is to investigate and compare the effect of the latest CHARMM and AMBER force fields(including bsc1 and OL15) on the B-DNA to A-DNA conversion through exploring the free-energy changes of the conversion process. The extended adaptive biasing force(eABF) method was utilized to perform the free-energy calculations. The results showed that the free-energy profiles characterizing the transition differ significantly for these two force fields. The AMBER force field performs better than the CHARMM force field in aqueous solution. The structure near the global minimum of the free-energy profile by the AMBER force field presents B-form, in agreement with the experimental results, while the most stable structure by the CHARMM force field locates between A- and B-form. Deep analysis of the radial distribution functions of the counterions around DNA reveals that the distribution of counterions in minor groove using the CHARMM force field is lower than that using the AMBER force field. Therefore, for the CHARMM force field, the repulsion of phosphates backbone could not be properly counteracted by counterions, as a result, the minor groove becomes wider, causing a slight conformational change towards A-form.

Key words: B-DNA, A-DNA, Conformational conversion, CHARMM force field, AMBER force field, Free-energy calculation

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